A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2
Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially ac...
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Published in | Frontiers in immunology Vol. 13; p. 918817 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Frontiers Research Foundation
01.07.2022
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 National Cancer Institute (NCI) LA-UR-23-25020 89233218CNA000001 National Institutes of Health (NIH) USDOE National Nuclear Security Administration (NNSA) Reviewed by: Mansi Srivastava, Purdue University Indianapolis, United States; Eleni Karakike, National and Kapodistrian University of Athens, Greece Edited by: Lucia Lopalco, San Raffaele Hospital (IRCCS), Italy This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology These authors share first authorship |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.918817 |